Serotonin-Mediated Synapsin Expression Is Necessary for Long-Term Facilitation of theAplysiaSensorimotor Synapse

Abstract

Serotonin (5-HT)-induced long-term facilitation (LTF) of the Aplysia sensorimotor synapse depends on enhanced gene expression and protein synthesis, but identification of the genes whose expression and regulation are necessary for LTF remains incomplete. In this study we found that one such gene is synapsin, which encodes a synaptic vesicle-associated protein known to regulate short-term synaptic plasticity. Both synapsin mRNA and protein levels were increased by 5-HT. Upregulation of synapsin protein occurred in presynaptic sensory neurons at neurotransmitter release sites. To investigate the molecular mechanisms underlying synapsin regulation, we cloned the promoter region of Aplysia synapsin, and found that the synapsin promoter contained a cAMP response element (CRE), raising the possibility that the transcriptional activator CREB1 mediates 5-HT-induced regulation of synapsin. Indeed, binding of CREB1 to the synapsin promoter was increased following treatment with 5-HT. Furthermore, increased acetylation of histones H3 and H4 and decreased association of histone deacetylase 5 near the CRE site is consistent with transcriptional activation by CREB1. RNA interference (RNAi) targeting synapsin mRNA blocked the 5-HT-induced increase in synapsin protein levels and LTF during a time window when basal synapsin levels were unaffected by RNAi. These results indicate that the 5-HT-induced regulation of synapsin levels is necessary for LTF and that this regulation is part of the cascade of synaptic events involved in the consolidation of memory.

Epigenetic mechanisms of chronic pain

“…Histone acetylation is thought to be more labile than DNA and histone methylation and to therefore represent a more transient cellular modification that quickly promotes gene expression in response to environmental stimuli [35, 36]. It is driven by histone acetyltransferases (HATs), which catalyze the addition of acetyl groups to histones and promote gene transcription [19,23].…”

MicroRNA-574 is involved in cognitive impairment in 5-month-old APP/PS1 mice through regulation of neuritin

“…Compared with the control group, the expression of miR-574-5p was obviously upregulated in primary hippocampal neuron stimulated by Aβ25-35 with qRT-PCR methods. The expression of synaptophysin (SYN), as a neuronal marker protein connected with the long-term potentiation (Hart et al, 2011;Evergren et al, 2007), and the expression of Nrn1 were both reduced in the primary hippocampal neuron treated with Aβ25-35 by immunofluorescence assay, and the protein expression of SYN and Nrn1 both decreased compared with the control group by western blot. And the expression of miR-574-5p also was upregulated in the hippocampal neurons from APP/PS1 mice compared with WT littermates, and it is directly showed the connection between miR-574-5p and APP/PS1 synapse impairment consistent with the result in the previous animal experiment.…”

Maggot learning and Synapsin function

“…These insights into Synapsin function were subsequently enriched in a number of ways (Benfenati, 2011): (1) Concomitant with the discovery of the requirement of Synapsin in non-associative short-term plasticity in Aplysia (Humeau et al, 2001), it was shown that serotonin induces Synapsin phosphorylation in Aplysia (Angers et al, 2002), likely via the cAMP-PKA pathway (Fiumara et al, 2004; see also Dolphin and Greengard, 1981) and/or the MAP kinase pathway (Giachello et al, 2010), and that these processes impact nonassociative short-term plasticity (Fioravante et al, 2007;Doussau et al, 2010;Giachello et al, 2010;Valente et al, 2012). Strikingly, it was recently reported that the synapsin gene of Aplysia features a CRE-recognition site, that serotonin induces de novo synthesis of Synapsin via the CREB1 pathway, and that this is required for nonassociative long-term plasticity (Hart et al, 2011).…”